Acceptable Donor Research Articles

Challenges encountered in conducting donor-based research: Lessons learned from the Donor Heart Study

Solid organ transplantation continues to be constrained by a lack of suitable donor organs. Advances in donor management and evaluation are needed to address this shortage, but the performance of research studies in deceased donors is fraught with challenges. Here we discuss several of the major obstacles we faced in the conduct of the Donor Heart Study-a prospective, multi-site, observational study of donor management, evaluation, and acceptance for heart transplantation. These included recruitment and engagement of participating organ procurement organizations, ambiguities related to study oversight, obtaining authorization for donor research, logistical challenges encountered during donor management, sustaining study momentum, and challenges related to study data management. By highlighting these obstacles encountered, as well as the solutions implemented, we hope to stimulate further discussion and actions that will facilitate the design and execution of future donor research studies.

Older-to-Older Living Kidney Transplantation: A New Paradigm

Older to older living kidney transplantation is an acceptable alternative to avoid dialysis, improve quality of life and maintain favorable long-term outcomes of patients with end-stage kidney disease. However, the management of these patients is complex and the acceptance of older donors and recipients to kidney transplantation remains controversial. The older recipients usually have several comorbidities that may complicate the postoperative course and increase the risk of end-stage kidney disease. We present a clinical case of living kidney transplantation between an older donor and recipient, both over 70 years old, who evolved to a stage 3 chronic kidney disease, without proteinuria, hypertension, or other complications, three years after transplantation. Our case reinforces favorable outcomes in older living transplantation, both for recipient and donor, as has been demonstrated in several published studies.

Using Information Available at the Time of Donor Offer to Predict Kidney Transplant Survival Outcomes: A Systematic Review of Prediction Models.

Statistical models that can predict graft and patient survival outcomes following kidney transplantation could be of great clinical utility. We sought to appraise existing clinical prediction models for kidney transplant survival outcomes that could guide kidney donor acceptance decision-making. We searched for clinical prediction models for survival outcomes in adult recipients with single kidney-only transplants. Models that require information anticipated to become available only after the time of transplantation were excluded as, by that time, the kidney donor acceptance decision would have already been made. The outcomes of interest were all-cause and death-censored graft failure, and death. We summarised the methodological characteristics of the prediction models, predictive performance and risk of bias. We retrieved 4,026 citations from which 23 articles describing 74 models met the inclusion criteria. Discrimination was moderate for all-cause graft failure (C-statistic: 0.570–0.652; Harrell’s C: 0.580–0.660; AUC: 0.530–0.742), death-censored graft failure (C-statistic: 0.540–0.660; Harrell’s C: 0.590–0.700; AUC: 0.450–0.810) and death (C-statistic: 0.637–0.770; Harrell’s C: 0.570–0.735). Calibration was seldom reported. Risk of bias was high in 49 of the 74 models, primarily due to methods for handling missing data. The currently available prediction models using pre-transplantation information show moderate discrimination and varied calibration. Further model development is needed to improve predictions for the purpose of clinical decision-making. Systematic Review Registration: https://osf.io/c3ehp/l.

Donor Utilization in the Recent Era: Effect of Sex, Drugs, and Increased Risk.

Background:Heart transplantation volumes have increased in recent years, yet less than a third of donors are typically accepted for transplantation. Whether donor sex, donor drug use, or perception of increased risk affects utilization for transplantation is unclear.Methods:The United Network for Organ Sharing database was queried for donors from January 1, 2007, to December 31, 2017. Donor toxicology was collected when available. Multivariate analysis was conducted to examine correlations with donor utilization.Results:Between January 1, 2007, and December 31, 2017, there were 87 816 heart donors aged ≥15 years. The mean age was 42.7±15.8 years, and 24 831 donors (28.3%) were utilized for heart transplantation. Subsequent analyses focused on donors between 15 and 39 years old.The strongest associations with donor acceptance were for male donor sex, blood type, hepatitis C antibody, donor age, left ventricular hypertrophy, and history of donor drug use. After removing hepatitis C, Public Health Service Increased Risk was identified as a strong negative predictor. Most positive drug toxicology results were associated with donor nonuse except for donors between 15 and 19 years of age. Exceptions included alcohol, marijuana, and cocaine. Opiates were associated with less utilization at all donor ages. The Public Health Service Increased Risk status was associated with significantly less utilization in all age groups except 15- to 19-year-old donors.Conclusions:While male donors were preferentially utilized, donors with drug use or those deemed Public Health Service Increased Risk were significantly less utilized for heart transplantation. Further consideration of such donors would be appropriate particularly as the demand for transplantation continues to increase.

Medical decisions in organ donors and heart transplant candidates with history of COVID-19 infection: An international practice survey.

BackgroundA growing proportion of transplant donors and recipients have a history of COVID‐19 infection. This study sought to characterize clinical practice after recipient or donor COVID‐19 infection.MethodsAn online survey was distributed to heart transplant clinicians through a professional society message board and social media. Responses were collected between September 29 and November 5, 2021.ResultsThere were 222 health care professionals (68% transplant cardiologists, 22% transplant surgeons, 10% other) across diverse geographic regions who completed the survey. While there was significant variation in donor acceptance, as it relates to past and current COVID‐19 infection, the respondents were fairly cautious: 28% would not typically accept a donor with a history of COVID‐19 regardless of the infection course and > 80% would not accept donors who had evidence of myocardial dysfunction during past COVID‐19 infection, or who died of COVID‐19 or its complications. The timing of candidate reactivation on the waiting list after COVID‐19 infection also varied and often diverged from scenarios addressed by social guidelines. Eighty‐one percent of the respondents felt COVID‐19 vaccine should be mandatory before transplant, but this rate varied by geographic region.ConclusionOur results reflect evolving experience of the heart transplant field at a time of lack of high‐quality evidence. In the absence of longer‐term outcome data for donors and transplant candidates with history of COVID‐19 infection, clinicians remain cautious; however, this approach will likely need to be refined as an increasing proportion of the population will continue to be infected with COVID‐19.

Prognostic impact of preoperative respiratory colonization on early-onset pneumonia after lung transplantation.

BackgroundThe number of lung transplantation procedures is rapidly increasing worldwide. Little is known about the effect of perioperative respiratory microbial colonization on pneumonia during lung transplantation. We evaluated the microbiome composition and incidence of early pneumonia in patients undergoing lung transplantation. We investigated factors related to post-transplant pneumonia (PTP) after lung transplantation.MethodsA retrospective analysis of patients subjected to lung transplantation between May 2013 and December 2019 was performed. Perioperative microbial colonization, and its relationship with early pneumonia, were examined in specimens from bronchial washing, bronchoalveolar lavage, and sputum aspiration before and after surgery. One-year mortality, as the primary outcome, was analyzed using the Kaplan-Meier curve model.ResultsAmong 76 patients who underwent lung transplantation, 34 donors (44.7%) and 28 recipients (36.8%) showed positive respiratory cultures with respect to preoperative respiratory colonization. A separate analysis of donors and recipients showed that 42 donors and 48 recipients were in respiratory non-colonized state, and 28 (53.8%) donors and 36 (69.2%) recipients survived 1 year after lung transplantation. Acinectobacter baumannii was the most common respiratory multidrug-resistant (MDR) pathogen. PTP was significantly lower in the survivor group (38.5% vs. 70.8%, P=0.009). Out of the recipients with preoperative respiratory colonization, 57.1% survived 1 year after lung transplantation. Patients with PTP had significantly higher 1-year mortality than those without PTP (P=0.009). Preoperative respiratory colonization of the recipients (P=0.010) and PTP patients (P=0.005) was associated with high 1-year mortality rate. Perioperative respiratory colonization of donors was not associated with the incidence of PTP and 1-year survival.ConclusionsPerioperative colonization of recipients was a powerful predictive factor for PTP, which was associated with 1-year mortality in patients subjected to lung transplantation. Our results suggest that donor acceptance criteria may change to better address potential shortages in organ donation.

Prevalence of Irregular Red Cell Antibodies in Healthy Blood Donors at a Stand-Alone Blood Centre in Gujarat

Background: Blood transfusion therapy involves multiple steps to ensure selection of safe blood component for transfusion. This includes testing for infectious markers, full ABO compatibility, free from any irregular red cell antibodies especially which are reacting at wide thermal amplitude and acceptable donor's red cell survival rates without destruction of recipient's red cells. Objective: This study was aimed to assess prevalence and type of irregular red cell antibodies in a large number of blood donor population at a standalone blood centre in Gujarat. Methods: This retrospective observational study included blood donor samples for antibody screening from January 2018 to March 2022. A total of 2,16,576 healthy blood donors including 2,00,493 (92.57%) males and 16,083 (7.43%) females were screened. Results: The prevalence of irregular red cell antibodies was 0.03 per cent in our donor population. Of the total 66 donors with red cell antibodies, 53(80.30%) had alloantibodies, 8(12.12%) had autoantibodies and 6 donors (9.09%) showed positive antibody screening with inconclusive results. We also found one case of cold antibody. Conclusion: Alloimmunization to red cell antigens is a challenging task for current transfusion practices. The antibody screening in blood donors may improve the quality and safety of blood transfusion in the recipients. It also reduces the risk of complications from incompatible blood transfusions. Keywords: antibody screening, allo-antibody identification, autoantibody, safe blood transfusion, hemolytic transfusion reaction.

Anatomical Gift Programs Continue to Meet Donor Demands of Anatomy Educators During the COVID‐19 Pandemic: Here’s How

INTRODUCTIONSchools of higher education across the US closed all operations and in‐person classes during the COVID ‐19 pandemic, significantly affecting laboratory‐based anatomy dissection courses and the anatomical gift programs (AGP) that support them. The purpose of this study was to investigate how the COVID‐19 pandemic affected AGP operations in the US. The researchers hypothesized that programs would modify donation acceptance criteria and that anatomy education demands for donors would be reduced during the first year of the pandemic.METHODS/ RESULTSThe researchers sent a Qualtrics survey to 135 AGP directors with a response rate of 28% (n=38). Respondents were from 26 states and included 28 AGPs operating for 25 years or longer and ten programs operational for 15 years or less. Six AGP’s (16%) stopped accepting donors for varying lengths of time secondary to the COVID‐19 pandemic during its first year, while 32 programs (84%) continued operations. Of the programs that remained operational, 81% (n=26) made modifications to donor acceptance policies, while 19% (n=6) maintained existing acceptance policies. Schools that made policy modifications for donor acceptance criteria reported changes, including heightened screening for symptoms of COVID‐19 at the time of donor registration and upon death and requiring a negative COVID test for the anatomical donor near the time of death. In addition, COVID‐19 infection was added to the existing list of disqualifying conditions for many programs. Some sites excluded donors from large group facilities (hospitals, long‐term care), and some declined any donors with respiratory infections at the time of death. Several programs (13%) stopped accepting those donors who were not registered with their AGP prior to the onset of the COVID pandemic.During COVID‐19, the demand for donors in anatomy education decreased significantly (p<0.05). Reasons for the reduced donor demand as reported by respondents included school closings and adjusted (smaller, shorter in time) laboratory sessions. These actions were taken because of concern for student/staff safety, reduced availability of appropriate personal protective equipment, and safety‐related student/faculty spacing needs.CONCLUSIONMost AGPs were operational during COVID‐19 and able to maintain donor needs for anatomy education. Further research is warranted into the long‐term effects on AGPs as the pandemic persists.

Hair‐Bearing Human Skin Organoids from Pluripotent Stem Cells: A Novel Source of Advanced Skin Substitutes for Wound Repair

Cutaneous injuries represent a major clinical challenge domestically and globally. Indeed, chronic wounds are estimated to affect the quality of life of nearly 2.5% of the United States population, and diabetic foot ulcers have a lethality nearly equivalent to that of all cancers combined. While skin grafts remain an important component in the care of both acute and non‐healing wounds alike, there are numerous drawbacks to such procedures, including lack of acceptable donor sites, morbidity associated with harvest, potential scarring at recipient sites, and graft loss. To these ends, advanced skin substitutes have been developed in efforts to overcome some of these obstacles, however existing modalities combining dermal and epidermal cell populations fail to develop skin appendages like eccrine glands and hair follicles critical for normal skin function. Thus, there is an unmet need for advanced cellular skin substitutes that more faithfully recapitulate native human integument.Our recent work reveals that co‐induction of epithelial and mesenchymal cell differentiation from human pluripotent stem cells gives rise to hair‐bearing skin organoids (SKOs) in vitro. These SKOs develop as spherical structures composed of mesenchymal cells surrounding stratified keratinocytes lining a central cystic cavity, producing hair follicles with bulbs oriented radially outward and hairs that grow into the cyst. Importantly, hairy human SKOs successfully engraft when applied to small incisions surgically created on the backs of immunocompromised nude mice, transitioning to a planar orientation with vertical hair outgrowth within 4‐5 weeks of transplant. Therefore, we hypothesized SKOs could similarly be applied to excisional wounds in a model system more akin to human injuries requiring skin grafts.Here, we demonstrate that hairy human SKOs applied to murine dorsal excisional wounds at 140 days post‐differentiation successfully take and undergo cystic‐to‐planar transition (CPT) within 5 weeks of surgery. We further show that SKOs xenografted at 80 days post‐differentiation, when hair‐germ‐like buds are visible in vitro but have not yet sprouted hairs, not only readily engraft and go through CPT, but also continue to develop hairs in vivothat show vertical outgrowth within the same time frame. Moreover, human SKOs xenografted at an earlier stage of development appear less macroscopically distinct from the surrounding host mouse skin than those at the later, hair‐bearing stage, suggesting transplant at earlier time points may yield improved cosmetic outcomes. Overall, our findings reveal human pluripotent stem‐cell derived SKOs may form the basis of a novel advanced skin substitute for clinical use, with future studies focused on exploring their utility in additional models of both acute and chronic wounds, as well as understanding the molecular and cellular mechanisms underlying CPT.

Evaluation and adjustment of screening algorithms for HBV, HCV, HIV and syphilis in an anatomical donation program for undergraduate education

Study objectiveUndergraduates and other users of anatomical donors are at risk of exposure to bloodborne pathogens. This study evaluated screening algorithms for hepatitis B and C virus, human immunodeficiency virus and Treponema pallidum during donor allocation and assessed the impact of postmortem time on hemolysis and how hemolysis affects test results and donor discard rate.MethodsFrom 2011‐2018, demographic data of donors, time of postmortem blood sampling, presence of sample hemolysis, serological test results (negative; active infection; false reactive screening test; historic infection; inconclusive; technically impracticable) and the actual donor allocation were collected.ResultsDonors (n=537) had a mean age of 77.53±13.67 year. Nine (1.68%) had test results indicative for active infection for hepatitis B (n=1) and C virus (n=2), human immunodeficiency virus (n=5) and Treponema pallidum (n=1). Negative screenings ranged from 74.67 to 97.58%, depending on the pathogen. Based on the screening algorithms, 479 (89.20%) donors should have been accepted. In practice, a donor acceptance rate of 91.20% was found. Analysis of potential donor allocation interpretation obstacles resulted in simplification of the testing algorithms and addition of a nucleic acid test to increase the reliability for identification of active (acute) human immunodeficiency virus infection. Hemolysis was more common when sampling was performed more than 24 hours after death (p&lt;0.001). Hemolytic samples more frequently showed a reactive or indeterminate human immunodeficiency virus test result (p&lt;0.001). Screening for human immunodeficiency virus and Treponema pallidum was technically more impracticable when hemolysis was present (p=0.042 and p=0.003, respectively). Donors with hemolytic blood samples were more often discarded (46.88%) compared to bodies with non‐hemolytic samples (6.32%) (p&lt;0.001).ConclusionsDespite the use of screening algorithms, many bodies used for undergraduate education have an inconsistent allocation. Simplified algorithms were made and are currently prospectively assessed. Early postmortem blood sampling is key as hemolysis can influence certain test results and donor allocation.

Myeloproliferative neoplasms – a global view

Myeloproliferative neoplasms – a global view

Outcomes of axillofemoral and aortofemoral bypass for intermittent claudication may be similar

Despite almost 40 years of experience with axillofemoral grafts, there remains an absence of clear guidelines for their use, especially in treating intermittent claudication (IC). This motivated Levin et al1Levin S.R. Farber A. King E.G. Beck A.W. Osborne N.H. DeMartino R.R. et al.Outcomes of axillofemoral bypass for intermittent claudication.J Vasc Surg. 2021; 75: 1687-1694Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar to examine the Vascular Quality Initiative (VQI) database to evaluate the appropriateness of axillofemoral bypass for IC. Although apparently their aim was not to compare axillofemoral bypass data with aortofemoral bypass grafts, much of their paper is devoted to such a comparison. On the basis of this evaluation, they first conclude that axillofemoral bypass is associated with significant perioperative morbidity, mortality, and long-term complications, and second, serious consideration should be given before its use for IC. Critical review posits that their second conclusion is correct and admirable, but the first may not be entirely accurate. In assessing an operative technique that involves a bypass graft, all preoperative, intraoperative, and postoperative variables and outcomes need to be considered to determine its efficacy and clinical benefit. Although the VQI is a formidable database, concerning axillofemoral bypass many confounding factors were not recorded. These include the status of the donor subclavian/axillary artery, the use of heparin surfaced grafts, postoperative surveillance protocols, and interventions to maintain patency of the donor artery. Indeed, recent papers2Samson R.H. Showalter D.P. Lepore M.R. Nair D.G. Dorsay D.A. Morales R.E. Improved patency after axillofemoral bypass for aortoiliac occlusive disease.J Vasc Surg. 2018; 68: 1430-1437Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar,3Hardouin S. Cheng T.W. Farber A. Kalish J.A. Jones D.W. Malas M.B. et al.Axillarybifemoral and axillary-unifemoral artery grafts have similar perioperative outcomes and patency.J Vasc Surg. 2020; 71: 862-868Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar have demonstrated excellent patency rates when heparin-bonded axillofemoral polytetrafluoroethylene grafts had been used or with axillary arteries that were proven normal or endovascularly treated to be, or remain, an acceptable donor vessel. Further, it is critical that if axillofemoral grafts are compared with the "gold standard" aortofemoral procedures, variables must be equivalent. In this report, patients undergoing axillofemoral grafts were more often older, female, had noncommercial insurance, ambulated with assistance, had a previous inflow bypass, ipsilateral leg bypass, peripheral endovascular intervention, and major amputation. Further, they were more often hypertensive, more likely to have coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, diabetes, anemia, and end-stage renal disease (P < .05 for all). Despite these significant risk factors, axillofemoral bypass was accompanied by a shorter length of stay, fewer pulmonary and renal complications, and, assuming these results, possibly lower cost. Further, despite these morbidities, they did not suffer more postoperative medical complications or operative mortality. Extensive comorbidities may also explain the difference in survivors’ amputation rate (5.2% vs 2%) and graft occlusion (7% vs 3.6%). However, the latter difference may also result from failure to use the more current heparin-bonded polytetrafluoroethylene or dual antiplatelet and statin therapy. Further, researchers must be leery of combined end points where one of its constituents significantly outweighs the others. For example, the authors reveal that 1-year ipsilateral reintervention/amputation/death was more likely with axillofemoral grafts, yet it is notable that occlusion/death and amputation/death were similar between cohorts. What then is the takeaway? First, appropriately surgeons who enter data into the VQI are more likely to use axillofemoral bypass grafts for high-risk patients. Second, even aortofemoral bypass grafts have significant morbidity and mortality. Therefore, the authors’ conclusion is correct that serious consideration should be given before axillofemoral bypass for IC. However, this conservative approach applies equally to aortofemoral bypass procedures. The opinions or views expressed in this commentary are those of the authors and do not necessarily reflect the opinions or recommendations of the Journal of Vascular Surgery or the Society for Vascular Surgery. Outcomes of axillofemoral bypass for intermittent claudicationJournal of Vascular SurgeryVol. 75Issue 5PreviewAlthough endovascular therapy is often the first-line option for medically refractory intermittent claudication (IC) caused by aortofemoral disease, suprainguinal bypass is often performed. Although this will often be aortofemoral bypass (AoFB), axillofemoral bypass (AxFB) is still sometimes performed despite limited data evaluating its utility in the management of IC. Our goal was to assess the safety and durability of AxFB performed for IC. Full-Text PDF

Reducing Donor Acceptance Practice Variation- Learnings from a Discussion Forum

<h3>Purpose</h3> Many acceptable donor hearts are turned down by pediatric centers with varying criteria for an acceptable donor. Advanced Cardiac Therapy Improving Outcome Network (ACTION) and Pediatric Heart Transplant Society (PHTS) centers convened a multi-institutional donor decision discussion forum (DDDF) aimed at assessing donor acceptance practice and reducing practice variation across centers. <h3>Methods</h3> The team hosted an hour-long monthly virtual DDDF among pediatric transplant centers across North America, UK and Brazil. Each call had two case presentations posing a donor decision challenge for the presenting center at the time of donor offer. Following each presentation, the attendee group was polled to obtain insight on donor acceptance practices after which the presenting center's decision was revealed. Then, group discussion occurred including a review of relevant literature and latest PHTS data related to the case. Metrics of participation, participant agreement with presenting center decision and impact on future decision making were collected and analyzed. <h3>Results</h3> Over 14 months, 23 cases were discussed; an average of 50 physicians, nurses and fellows attended each call. The mean donor age was 8.2 ± 3.3 years (28.6% infants, 52.4% young adults), and the mean recipient age was 8.36 ± 3.3 years (27.3% infants and 40.9% teenagers). Reason for listing was congenital heart disease in 10, cardiomyopathy in 5 and retransplantation in 3. Risk factors influencing decision making included size discrepancy (4), Infection (5), COVID (2), Prolonged QT (2), Malignancy (2), Drugs (2), Distance (1) Prolonged CPR (1) high inotrope use (1) Dialysis (1) Diabetes (1) HLA mismatch (1). Of the 23 cases, 15 were declined by presenting center. Donor characteristics influenced 45% of the decisions and recipient only 20%, with rest being other factors. Participants agreed with the decision made by the presenting center 55% of the times. The post-presentation discussion resulted in 30% of participants changing their original decision. <h3>Conclusion</h3> DDDF identified significant variation in pediatric donor acceptance practices; with donor characteristics most influential in decision-making. Given that the discussions changed decisions in 1/3^rd of the participants, DDDF may be a useful format to reduce practice variation, provide education to decision makers and eventually increase donor utilization.

Donor Utilization in the Recent Era: Effect of Sex, Drugs and Increased Risk

<h3>Purpose</h3> Recently, the number of organ donors has increased as have the number of heart transplants in the United States. However, the percentage of offered donors utilized for transplantation has remained low in prior reports. Whether this has changed in the last 15 years is not known. The effect of donor increased risk status and drug use on donor acceptance is also unclear. <h3>Methods</h3> The UNOS registry was queried for all donors offered for transplantation between 1/1/2007 and 12/31/2017. Donors utilized for heart transplant were compared to rejected hearts including demographics, hepatitis C serology (HCV), Public Health Service Increased Risk (PHSIR) designation as well as history of drug use and positive toxicology. The UNOS Tox Score (UTS) was the sum of positive historical drug use variables in the UNOS registry and the Measured Tox Score (MTS) was the sum of positive donor toxicology categories. Comparisons were made by Pearson Correlation and Chi Square. <h3>Results</h3> Over the 10 years of the study, 87816 donors aged 15 or older were offered for transplantation. In 2007 there were 7504 donors offered, increasing by 28.9 % to 9669 donors in 2017. The median donor age dropped from 45 years (IQR 28-55) in 2007 to 42 (IQR 29-54) in 2017. Heart donor acceptance increased marginally from 26.4 % in 2007 to 30.1 % in 2017 (p<0.0001 across years). Nominal logistic regression analysis revealed the strongest predictors of donor non-use were older donor age, female gender, blood type, HCV, and left ventricular hypertrophy. After excluding demographics and hypertrophy, the strongest predictors were HCV, and positive UTS or MTS, followed by PHSIR status. HCV hearts were utilized less than 1 % until 2017 when 3.5 % of such donors were accepted. The analysis was repeated limiting donor age to 39 or less, and donor age, PHSIR and UTS/MTS were still strong discriminators between the accepted and discarded heart groups. Similar results were obtained with donor age restricted to 15-30 years (n=24347, 53.9 % of hearts accepted), though more donors were accepted. <h3>Conclusion</h3> Even in the last decade, the usage of offered heart donors continues to be very low. Given evidence of safety, factors such as PHSIR, drug use and HCV should not be barriers to utilization of heart donors, particularly at younger ages.

How High is Too High? Analysis of Donor Inotrope Support in Pediatric Heart Transplantation

<h3>Purpose</h3> While the impact of donor inotrope use on post-transplant outcomes has been studied, a dose dependent relationship has not yet been established. We use donor Inotrope Score (dIS) to examine the impact of inotrope quantity on post-transplant outcomes in pediatric heart transplant recipients. <h3>Methods</h3> The United Network for Organ Sharing (UNOS) database was used to identify deceased donors <40 years between 2000-2019. Available dopamine, dobutamine, and epinephrine doses were used to calculate dIS. Donors were divided into two groups: Low dIS (score: ≤10), and High dIS (score: 10-30). Only 3% of dIS were above >30 and were excluded from the analysis. Post-transplant survival (PTS) and pediatric donor utilization (pDU) were compared. <h3>Results</h3> Of the total (n=4870), 28% (n=1373) recipients received an inotrope supported donor heart: Low dIS, n=1209 (88%); High dIS, n=164 (12%). High dIS patients were younger and lighter than Low dIS patients (p<0.01 for both). At transplant, high dIS recipients more often had renal dysfunction (eGFR) (40% vs 28%, p=0.003), required ECMO (11% vs 6%, p<0.01), and were on the ventilator (29% vs 18%, p<0.01). Donors did not differ in terms of Left Ventricular ejection fraction (LVEF) (63% vs 60%, p=0.50), ischemia time (3.8hours [2.3-4.3] vs 3.6 [3-4.4], p=0.26), or steroid use (69% vs 75%, p=0.10). Epinephrine use was more common in the high vs the low dIS group (29% vs 7%, p<0.01). PTS was worse in the high dIS vs low dIS group (1 year-83% vs 90%, p<0.05). On MV analysis, high dIS was a significant predictor of mortality (HR:1.4, CI:1.1-1.8). When broken down by age groups, high dIS was only significant for age <2 years (HR:1.8, CI:1.2-2.5). pDU was worse in dIS ≤10 compared to donors not on inotropes (66% vs 76%, p<0.01). <h3>Conclusion</h3> High dose inotrope use only impacts mortality in recipients <2 years of age. Although post-transplant mortality is not impacted by low dose inotrope use, heart utilization was worse in this group when compared to those not on inotropes. Acceptance of pediatric donors with low inotrope exposure could increase heart utilization, without negatively impacting survival.

Nasal Reconstruction with Paramedian Forehead Flaps at University of Port Harcourt Teaching Hospital and Professor Kelsey Harrison’s Hospital, Port Harcourt, South-South, Nigeria: Our Experience

Background: Nasal reconstruction is one of the most challenging head and neck surgeries. It demands a thorough understanding of the anatomy of the nose by the surgeon who will do a meticulous planning and have an excellent surgical skill in order to achieve good outcomes. The forehead flap is a veritable option for reconstruction with acceptable colour match and donor site morbidity. In our environment, the skill is not yet readily available. Objective: To share our experience with the use of paramedian forehead flap in the reconstruction of complex defect of the nose in the two referral hospitals in the South-South zone of Nigeria. Method: This is a retrospective study which involved analysis of the data obtained from the three male patients treated in two referral hospitals from the month of May 2013 to April 2015. Three cases of nasal defects reconstructed with paramedian forehead flaps were presented. The three cases designated 1, 2 and 3 here, presented with full thickness defects of varying number of aesthetic subunits, resulting from matchete cut, high velocity gunshot and human bite respectively. In all the cases, the three-dimensional form of the nose was achieved, with patent nasal passage which was indeed a pretty challenge. The outcome, including the donor site morbidity, was acceptable to all the patients, so were satisfied. Result: The complex defects, involving the lining, the skeletal support and the cover, in the three male patients were reconstructed using paramedian forehead flap, and both lining and skeletal support were provided. The outcome in terms of the colour match, texture, patency and tip projection were acceptable to the patients. Conclusion: Paramedian forehead flap remain the workhorse for nasal reconstruction and the expertise is available in the Port Harcourt to serve the populace in the South-South region of Nigeria.

When is Significant Left Ventricular Hypertrophy Acceptable for Donor Heart Selection

<h3>Purpose</h3> Extended criteria of donors for heart transplant (HTx) include many factors, such as left ventricular hypertrophy (LVH), decreased LVEF, older donor age, inotrope dependence, as well as gender and size mismatch. It has also been reported that various combinations of extended criteria risk factors appear to have worse outcomes depending on severity of the extended criteria characteristic. We sought to assess if severity of LVH with acceptable donor age and ischemic time is associated with increased mortality. <h3>Methods</h3> Between 2010 and 2020, we assessed 156 donor hearts with varying degrees of LVH defined as left ventricular septal thickness greater than 1.2 cm. Donor hearts were then divided into those that had IVS between 1.2 to <1.3 cm, 1.3 to <1.5 cm, ≥1.5 cm. In addition, an assessment was made for the same LVH groups versus donor age categorized as donor age ≥50 years old and donor ischemic time >240minutes. <h3>Results</h3> Severity of LVH with donor age <50 years and ischemic time <240 min appear to have acceptable 1-year survival. However, older donor age/long ischemic time with LVH are higher risk for 1-year mortality. (see table) <h3>Conclusion</h3> Severe LVH (IVS >1.5 cm) in donor hearts appears to be acceptable with donor age <50 years and ischemic time <240 minutes.

Musculocutaneous Latissimus Dorsi Phalloplasty

The treatment of gender dysphoria consists of psychiatric evaluation, initiation of hormonal therapy, and the final step in an individual's transition, performing gender-affirming surgery. Construction of the neophallus is one of the most demanding tasks in genital affirming surgery of transgender men. The main objectives of phalloplasty are to achieve a cosmetically acceptable and functional phallus, with a neourethra that allows voiding in standing position, sufficient length and strength for possible penetrative intercourse, preserved tactile and orgasmic sensation, and acceptable donor site morbidity. The musculocutaneous latissimus dorsi flap has reliable and suitable anatomy (good size, volume, and length of neurovascular pedicle) to meet the esthetic and functional requirements of neophallus reconstruction. Despite many advantages, the main disadvantage of this flap is the lack of sensitivity. Although the radial free forearm flap technique is the most commonly performed procedure, musculus latissimus dorsi flap is an acceptable choice in gender-affirming surgery.

Evaluation of Safety and Effectiveness of the Paragonix™ SherpaPak Cardiac Transport System in Donation After Circulatory Death Heart Transplantation (clinicaltrials.gov Identifier: Nct05038943)

Purpose To evaluate the safety and effectiveness of The Paragonix SherpaPak™ Cardiac Transport System (CTS) in the transportation of cardiac allografts recovered from donors after circulatory death (DCD) with thoracoabdominal normothermic regional perfusion (TA-NRP). Methods Institutional Review Board (IRB#0478-21-FB) approved this single center pilot study for a total number of 5 heart transplants. The study is designed as a single arm feasibility study. The study opened for enrollment on September 15th 2021, the anticipated duration is one year. All patients included in DCD NRP study (NCT04615182) will be consented to participate in DCD NRP Paragonix study (NCT05038943). Inclusion and exclusion criteria are summarized in Table 1. Donor organs will be procured after no more than 30 minutes of warm ischemia (defined as a time period commencing from systolic blood pressure < 50 mmHg to the start of reperfusion) and resuscitated in-situ with TA-NRP in accordance with the approved institutional protocol. Criteria for donor acceptance for transplantation are depicted in Table 2. Allografts will be transported from a donor site to recipient center with the SherpaPak™ CTS. All implantation procedures will be performed at our institution. Recipients will receive standardized immunosuppression and infection prophylaxis and will undergo rejection surveillance with serial endomyocardial biopsies. Endpoints Primary outcome is primary graft dysfunction (PGD) at 24, 48, and 72 hours (using ISHLT definition). Secondary outcomes are: need for cardioversion or pacing to restart transplanted heart; vasoactive-inotropic score at 24, 48, and 72 hours (dopamine dose (µg/kg/min) + dobutamine dose (µg/kg/min) + 100 x epinephrine dose (µg/kg/min) + 100 x norepinephrine dose (µg/kg/min); intensive care unit and hospital length of stay; and 30-day, 90-day, 1-year survival. To evaluate the safety and effectiveness of The Paragonix SherpaPak™ Cardiac Transport System (CTS) in the transportation of cardiac allografts recovered from donors after circulatory death (DCD) with thoracoabdominal normothermic regional perfusion (TA-NRP). Institutional Review Board (IRB#0478-21-FB) approved this single center pilot study for a total number of 5 heart transplants. The study is designed as a single arm feasibility study. The study opened for enrollment on September 15th 2021, the anticipated duration is one year. All patients included in DCD NRP study (NCT04615182) will be consented to participate in DCD NRP Paragonix study (NCT05038943). Inclusion and exclusion criteria are summarized in Table 1. Donor organs will be procured after no more than 30 minutes of warm ischemia (defined as a time period commencing from systolic blood pressure < 50 mmHg to the start of reperfusion) and resuscitated in-situ with TA-NRP in accordance with the approved institutional protocol. Criteria for donor acceptance for transplantation are depicted in Table 2. Allografts will be transported from a donor site to recipient center with the SherpaPak™ CTS. All implantation procedures will be performed at our institution. Recipients will receive standardized immunosuppression and infection prophylaxis and will undergo rejection surveillance with serial endomyocardial biopsies. Primary outcome is primary graft dysfunction (PGD) at 24, 48, and 72 hours (using ISHLT definition). Secondary outcomes are: need for cardioversion or pacing to restart transplanted heart; vasoactive-inotropic score at 24, 48, and 72 hours (dopamine dose (µg/kg/min) + dobutamine dose (µg/kg/min) + 100 x epinephrine dose (µg/kg/min) + 100 x norepinephrine dose (µg/kg/min); intensive care unit and hospital length of stay; and 30-day, 90-day, 1-year survival.

Normothermic Regional Perfusion in Cardiac Transplantation: Developing a Program

<h3>Purpose</h3> Due to donor heart scarcity, heart failure patients are placed on a waitlist for transplantation. Efforts to expand the donor pool are essential to reduce waitlist mortality and add quality of life years. To increase organ utilization and transplantation our institution focused on innovations to allow DCD donor heart transplantation. Our program began utilizing DCD hearts in August 2020 as part of a clinical trial assessing direct procurement and machine perfusion technology. Following research on Normothermic Regional Perfusion (NRP) for DCD organ procurement and assessment, we established a clinical team to utilize this procurement strategy. <h3>Methods</h3> Our NRP program development was led by the Surgical Director and consisted of advanced heart failure fellows, transplant Nurse Practitioner, and transplant recovery specialists. The NRP program was developed in 4 phases. Phase 1: Research and concept development, IRB and and ethics review, and administration approval of NRP. Phase 2: NRP protocol development, donor acceptance criteria, and transportation logistics. Phase 3: Development of mobile cardio-pulmonary bypass system including supplies, specialized training, and construction of NRP procurement team consisting of five trained professionals. Phase 4: Dissemination of NRP protocols and focused education session for OPO and transplant center personnel. After completion of the first NRP heart transplant, all OPO leadership within our DSA were notified of our NRP program activation. <h3>Results</h3> The first remote NRP cardiac case was performed in May 2021 within our local DSA yielding a successful transplant. Our program year to date has completed 28 NRP procurement donor runs; yielding 20 transplants, with 8 aborted (6 did not expire, 1 decline due to quality, and 1 declined due to logistical issues). At present our program has 100% NRP transplant survival and our our annual transplant activity increased by 38%. <h3>Conclusion</h3> The structured development of an NRP program increased transplant volume with excellent short-term outcomes by utilizing previously discarded donor hearts.